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Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

In rectal cancer treatment, preoperative radiotherapy has led to reduction of local recurrence, but it is associated with morbidity and increased risk for secondary tumours. Matrix metalloproteinases (MMPs) are associated with tumour progression through tissue remodeling. The aim of this study was to investigate tissue remodeling after preoperative radiotherapy and to explore possible correlations with clinical outcome.

Materials and methods

Ninety-one patients scheduled for rectal cancer surgery were included; 49% received preoperative radiotherapy three-field treatment, 5 × 5 Gy. Blood samples and biopsies from tumour and adjacent mucosa were taken during surgery. Biopsies and plasma were assayed with ELISA for MMP-1, MMP-2 and MMP-9. Clinical outcome was reviewed focusing on infections, perineal healing, fistula formation, anastomotic dehiscence, small bowel obstruction, local recurrence and distant metastases.

Results

Compared to non-irradiated mucosa, MMP-2 (p < 0.0001), MMP-1 (p = 0.03) and MMP-9 (p = 0.04) were significantly higher in irradiated normal mucosa. Tumour tissue had higher levels of MMP-2 if irradiated (p < 0.0001). A correlation between MMP-2 levels and wound infection (p = 0.02) as well as fistula formation (p = 0.04) was found. MMP-1 in mucosa (p = 0.02) and tumour (p = 0.04) were higher in patients developing distant metastases. Plasma levels were not influenced by irradiation, but MMP-2 was higher in patients who were later developing distant metastases (p = 0.007).

Conclusions

Extracellular matrix remodeling after radiotherapy seems to be correlated to postoperative morbidity; MMP-2 is associated with both wound infections and fistula formation. High levels of MMP-1 in tumour and mucosa as well as MMP-2 in plasma may be correlated to risk of developing distant metastases.

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Acknowledgements

The authors are indebted to the following individuals for their contributions: Tomas Seidal, MD, Ph.D., for performing histologic examinations of our biopsies; Lena Holmdahl, MD, Ph.D., Jan Dalenbäck MD, Ph.D., and Kristina Ticehurst, MD, Ph.D., for their valuable comments and inspiring discussions; Martin Gellerstedt for the inspiring statistical discussions; and Ingrid Palmgren for the excellent laboratory work. We also acknowledge the support through funds from the following institutions: Göteborg University; Halland’s Research Council; Gothenburg Medical Society; Swedish Research Council; JK-fonden, Gothenburg; and Assar Gabrielsson Foundation.

Conflict of interest statement

None of the authors has any conflict of interest in the subject matter.

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Authors and Affiliations

  1. Department of Surgery, Sahlgrenska University Hospital/Östra, Göteborg University, Gothenburg, Sweden

    Eva Angenete, Marcus Langenskiöld & Peter Falk

  2. Department of Surgery, Kungsbacka University Hospital, Gothenburg, Sweden

    Marie-Louise Ivarsson

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  1. Eva Angenete
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  2. Marcus Langenskiöld
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  4. Marie-Louise Ivarsson
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Correspondence to Eva Angenete.

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Angenete, E., Langenskiöld, M., Falk, P. et al. Matrix metalloproteinases in rectal mucosa, tumour and plasma: response after preoperative irradiation. Int J Colorectal Dis 22, 667–674 (2007). https://doi.org/10.1007/s00384-006-0225-3

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